BACKGROUND: Amyotrophic lateral sclerosis (ALS) coexisting with chorea is very rare.
METHODS: We present the case of a 48-year-old man with ALS and chorea; the diagnostic certainty was high based on clinical examination results. Combining the data from literature, we analyzed the characteristics of patients with ALS and chorea. We found that ALS coexisting with chorea is very rare, but is often hereditary with a genetic mutation. Most patients with ALS and chorea are caused by abnormal amplification of a CAG sequence in the HTT gene, and these patients have a mild course of disease. The FUS, VCP, and SETX genes also have low mutation frequencies in patients with ALS and chorea.
CONCLUSIONS: The abnormal amplification of a CAG sequence in the HTT gene in ALS with chorea has an obvious familial genetic tendency, and most patients have a mild disease course.

Microsatellites (or short-tandem repeats (STRs)) are widely used in anthropology and evolutionary studies. Their extensive polymorphism and rapid evolution make them the ideal genetic marker for dating events, such as the age of a gene or a population. This usage requires the estimation of mutation rates, which are usually estimated by counting the observed Mendelian incompatibilities in one-generation familial configurations (typically parent(s)-child duos or trios). Underestimations are inevitable when using this approach, due to the occurrence of mutational events that do not lead to incompatibilities with the parental genotypes (\'hidden\' or \'covert\' mutations). It is known that the likelihood that one mutation event leads to a Mendelian incompatibility depends on the mode of genetic transmission considered, the type of familial configuration (duos or trios) considered, and the genotype(s) of the progenitor(s). In this work, we show how the magnitude of the underestimation of autosomal microsatellite mutation rates varies with the populations\' allele frequency distribution spectrum. The Mendelian incompatibilities approach (MIA) was applied to simulated parent(s)/offspring duos and trios in different populational scenarios. The results showed that the magnitude and type of biases depend on the population allele frequency distribution, whatever the type of familial data considered, and are greater when duos, instead of trios, are used to obtain the estimates. The implications for molecular anthropology are discussed and a simple framework is presented to correct the naïf estimates, along with an informatics tool for the correction of incompatibility rates obtained through the MIA.

BACKGROUND: Until recently, the survival rate in patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) was approximately 30%. Tyrosine kinase inhibitors (TKIs), which are a new class of drugs that target BCR-ABL fusion protein, have shown to be effective in treating Ph+ ALL in adults. However, the resistance mechanisms that promote the disease recurrence have altered the initial success of these revolutionary agents.
METHODS: A 71-year-old Chinese female patient who suffered from severe shoulder and back pain for 1 week.
METHODS: The patient was diagnosed with Ph+ ALL (B-cell) because of the following items. Complete blood count showed extremely abnormal white blood cell count (26.26×109/l), hemoglobin concentration (65 g/l) and platelet count (14×109/l). And because that Bone marrow aspirate showed 72.5% lymphoblasts and 59.30% lymphoblasts were confirmed by flow cytometry (FCM). At mean time, Real-time fluorescent quantitative PCR analysis confirmed that the P190 BCR/ABL fusion gene expression was 5.9%. Karyotype analysis indicated the following: 45, XX, -7, t (922) (q34; q11) [cp3].
METHODS: The patient was treated with chemotherapy and different TKIs including imatinib, dasatinib, ponatinib, and bosutinib.
RESULTS: The patient achieved complete remissions with different TKIs after diagnose but relapsed afterward and died of infection.
CONCLUSIONS: Multidrug-resistant mutations within the BCR-ABL1 kinase domain are an emerging clinical problem for patients receiving sequential TKIs therapy. Acquisition of E255K/V-inclusive mutations is usually associated with ponatinib resistance, thus it is necessary to screen out new real pan-inhibitor compounds for all BCR/ABL mutations and figure out the potential efficacy of asciminib-based drug combinations in the future.

Autosomal short tandem repeats (asSTR) serve as genetic markers for discriminating individuals and have been extensively used for criminal investigations as well as the establishment of genetic relationships. Tri-allelic pattern usually occurs due to chromosomal duplication, trisomy, and chimerism during mitotic division, but a false tri-allelic pattern at the D7S820 locus was encountered in our laboratory during the analysis of a case exhibit. DNA isolation from exhibit for profiling was done as per manufacturer\'s protocol. This is the first report which observed false tri-allelic pattern (10, 11, 14.1 allele) on D7S820 locus by analysis with GlobalFiler™ PCR Amplification Kit in Indian population. Findings were re-confirmed using other available asSTR kits in the laboratory, viz., AmpFLSTR™ Identifiler™ Plus PCR Amplification Kit and PowerPlex® Fusion 6C System. Two alleles (10, 11) found at D7S820, apart from SE33 marker, showed homozygous condition, but one Off Marker (OMR) peak was observed before start of SE33 marker region with the analysis using PowerPlex® Fusion 6C System. As it has been confirmed that the OMR allele belongs to the SE33 locus, this could be possible because of the adjacent locations of the D7S820 and the SE33 in the GlobalFiler® PCR amplification kit. 14.1 allele appeared within the allelic window of D7S820. The false tri-allelic pattern was due to the overlapping of SE33 marker allele (1.2 repeat) with bin window of D7S820 Marker. This finding might create confusion for the establishment of genetic relationships. We, therefore, conclude that such uncommon observations with rare events should be carefully investigated and interpreted.

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung carcinoma (NSCLC), which characterized by insensitive to conventional radiotherapy and chemotherapy and poor prognosis. Except MET exon 14 alterations and other oncogene mutations, PSC commonly harbor high tumor mutational burden (TMB) and high level of PD-L1, which provide new therapeutic opportunities. Toripalimab (JS001) is IgG4 monoclonal antibody targeting PD-1, which has been approved for treatment of patients with metastatic melanoma after previous systemic therapy. PD-1 combined with radiotherapy has been tried in several cancer types.
We reported a case of a PSC patient with PD-L1 overexpression responding to toripalimab and after progression the patients also benefits from toripalimab combined with local radiotherapy, which provides a promising option for PSC patients.
This case provides the evidence of the effective role of toripalimab and PD-1 combined with local radiotherapy in PSC patients, which was the first application as far as we know.

To compare the frequencies of somatic homologous recombination (HR) gene mutations identified in next-generation sequencing (NGS) genomic profiling of uterine serous carcinomas (USCs) and high-grade serous ovarian carcinomas (HGSOCs).
Data for this analysis was obtained from AACR Project GENIE, a multi-institutional dataset of clinical-grade NGS genomic profiling results for many cancer sites and histologic subtypes, through cBioPortal. Patient/specimen groups used for analysis were USC and HGSOC. 14 HR genes were queried for each group with respect to mutation frequency. For each HR gene, the difference in mutation frequency between the two groups was evaluated using Fisher\'s exact test. The threshold for statistical significance was p-value < .05.
In the USC group, there were 457 samples from 451 patients. In the HGSOC group, there were 1537 samples from 1515 patients. The most frequently mutated HR gene for USC was BRCA2 (4.84%) and for HGSOC was BRCA1 (9.07%). Mutation frequency was significantly different between USC and HGSOC for BRCA 1 (p < .001) and BRCA2 (p = .0379). For the 12 non-BRCA HR genes, mutation frequency was not significantly different between USC and HGSOC. The rate of patients with at least one HR gene mutation in their profiled tumor was 16.85% for USC and 25.21% of HGSOC. Most USC patients with a somatic HR mutation had only one HR gene mutated.
Somatic HR gene mutations were commonly identified in NGS genomic profiling of USC. Mutation frequencies for non-BRCA HR genes were not significantly different between USC and HGSOC. These data add to the growing rationale for HR deficiency tumor testing and targeting (e.g., with PARP inhibitors) in future clinical trial development for women with USC.

Mixed corticomedullary tumor is an adrenal tumor intermixed with cortical and medullary cells. It is extremely rare with unclear tumorigenesis. We reported a 32-year-old female, manifested with typical Cushing\'s syndrome and hypertension, to be diagnosed with right huge adrenal mixed corticomedullary tumor (8.8 cm). Right adrenalectomy was done to document the tumor intimately admixed with adrenal cortical adenoma and pheochromocytoma by biochemistry and immunohistochemistry. A case-control study was designed to explore the tumorigenesis of mixed corticomedullary tumor by whole exome sequencing. Expression of the stemness markers was controlled by a tissue array of 80 adrenal tumors. Overall, 1559 identical variants coexisted in parts of adrenal cortical adenoma and pheochromocytoma, which mainly (85.8%) originated from germline mutations. These enriched mutations were engaged in stemness control, coherent with substantial expression of the stemness markers (SOX2, CD44 and OCT4) in both parts. The differential stemness expressions were demonstrated in other adrenal tumors as well. The germline mutations were also enriched in signaling involving cancer proliferation, hypoxia inducible factor-1, focal adhesion and extracellular matrix receptor interaction. Somatic mutations affecting mitogen-activated protein kinase signaling, glycolysis and the citrate cycle were found in some tumor elements. This is the first study to verify the rare mixed corticomedullary tumor by molecular and genetic evidence to link with its phenotype. Germline mutations involving the stemness regulation and cancer proliferative signaling may drive intermixed tumor formation. Somatic mutations related to glycolysis and the citrate cycle may contribute to greater tumor outgrowth.

BACKGROUND: Pathogenic variants (PVs) of BRCA genes entail a lifetime risk of developing breast cancer in 50-85% of carriers. Their prevalence in different populations has been previously reported. However, there is scarce information regarding the most common PVs of these genes in Latin-Americans. This study identified BRCA1 and BRCA2 PV frequency in a high-risk female population from Northeastern Mexico and determined the association of these mutations with the patients\' clinical and pathological characteristics.
METHODS: Women were divided into three groups: aged ≤ 40 years at diagnosis and/or risk factors for hereditary breast cancer (n = 101), aged > 50 years with sporadic breast cancer (n = 22), and healthy women (n = 72). Their DNA was obtained from peripheral blood samples and the variants were examined by next-generation sequencing with Ion AmpliSeq BRCA1 and BRCA2 Panel using next-generation sequencing.
RESULTS: PVs were detected in 13.8% group 1 patients (BRCA1, 12 patients; BRCA2, 2 patients). Only two patients in group 2 and none in group 3 exhibited BRCA1 PVs. Variants of uncertain significance were reported in 15.8% patients (n = 16). In group 1, patients with the triple-negative subtype, PV frequency was 40% (12/30). Breast cancer prevalence in young women examined in this study was higher than that reported by the National Cancer Institute Surveillance, Epidemiology (15.5% vs. 5.5%, respectively).
CONCLUSIONS: The detected BRCA1 and BRCA2 PV frequency was similar to that reported in other populations. Our results indicate that clinical data should be evaluated before genetic testing and highly recommend genetic testing in patients with the triple-negative subtype and other clinical aspects.

Rambaut et al show that the erratum to our report on Ebola virus Makona evolution not only corrected sample dates modified by others in GenBank but also corrected an additional transcriptional error in our original analysis. We agree with their observation that both factors contributed to our revised evolutionary rate estimate but continue to stand by our revised estimate and conclusions.

Hoenen et al (Reports, 3 April 2015, p. 117; published online 26 March) suggested that the Ebola virus Makona responsible for the West African epidemic evolved more slowly than previously reported. We show that this was based on corrupted data. An erratum provided a rate compatible with the initial and later, more precise, estimates but did not correctly state the nature of the error.